Spinocerebellar ataxia type 3 mimicking multiple system atrophy: late onset, parkinsonism, and atypical features

Abstract

Case Presentation: A 58-year-old man presented with progressive postural instability, gait ataxia, and vertigo beginning at age 54. He subsequently developed diplopia during visual effort and paroxysmal episodes of ascending cervical paresthesia associated with scintillating scotomas. There was no known family history. Neurological examination revealed a prominent cerebellar syndrome characterized by tetrasegmental dysmetria, dysdiadochokinesia, multidirectional nystagmus, and ataxic gait, in addition to asymmetric extrapyramidal signs on the left side (bradykinesia and rigidity). Brain magnetic resonance imaging demonstrated cerebellar and brainstem atrophy, with a suggestion of a “hot cross bun” sign in the pons. Based on this phenotype, multiple system atrophy was initially suspected. However, molecular analysis identified a pathogenic expansion in the ATXN3 gene (67 CAG repeats), confirming spinocerebellar ataxia type 3. The patient showed progression of ataxia with persistence of parkinsonism. Discussion: Spinocerebellar ataxia type 3 exhibits marked phenotypic heterogeneity, typically with earlier onset and positive family history. This case highlights several atypical features, including late onset, absence of recognized family history, asymmetric parkinsonism, and neuroimaging findings suggestive of multiple system atrophy. The possible “hot cross bun” sign, classically associated with multiple system atrophy, further contributed to the diagnostic challenge. Additionally, sensory manifestations and visual phenomena are not typical features of this condition. Genetic confirmation was crucial for etiological diagnosis, underscoring the importance of molecular testing in cerebellar syndromes even when another neurodegenerative disorder is strongly suspected. Final Comments: This case underscores the potential of spinocerebellar ataxia type 3 to mimic other neurodegenerative disorders, particularly multiple system atrophy. Clinical and radiological variability may hinder diagnosis based solely on phenotypic features. A systematic approach combined with genetic testing is essential in the evaluation of late-onset ataxias, enabling accurate diagnosis, appropriate genetic counseling, and improved understanding of the disease spectrum.